Area of research

Summary

As a structural biologist, I am interested in understanding biological systems at a molecular level. This is achieved by primarily using the technique of protein crystallography. A principal focus of our studies is the study and exploitation of proteins central to human disease. Our work is interdisciplinary, encompasses both basic and applied studies, and we work in close collaboration with a wide range of academic and industrial groups.

Career research highlights include:

The first structure of a lipase [Nature(1989) 343, 767-770], and two fungal amylases [Biochemistry 29, 6244-6249]. These structures have since contributed to protein engineering studies resulting in improved recombinant products with both medical and commercial applications.

HIV Proteins: Studies of the HIV receptor, CD4 [Science(1989) 260, 979-983], and the integrase enzyme from the virus [TIBTech,15, 167-172], a challenging drug target on which we worked closely with both Glaxo and Proteus, a small UK-based biotechnology company. From these studies a strong interest in structure-based drug design techniques emerged.

Immune System proteins: We worked with Celltech to determine a number of engineered antibody structures [J. Mol. Biol. (1992) 227, 253-264; Proteins SF&G(1997) 29, 161-171] which contributed to the development of products now commercialised by Celltech as diagnostic and therapeutic reagents for the treatment of colonic and breast cancers. Our fortuitous discovery that recombinant forms of the CD2 receptor could adopt more than one protein fold [PNAS(1995) 92, 7337-7341] provided us with a unique opportunity to probe the folding pathway and evolution of immunoglobulin domains [Nature Struct. Biol. (1998) 5, 778-782; J. Mol. Biol.(1999) 285, 1857-1867].